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a pair of Velcro strips that bind to one another. The lung is rich in ACE-2 receptors, so it’s quite easy for me to establish myself there. After docking onto an ACE-2 receptor, I rely heavily on special enzymes called furins and cathepsins for slicing away parts of my S-protein. These enzymes act on a site in the S1/ S2 region and another in the S2 region. Once both cleavages have occurred, the S2 is ‘locked and loaded’ to anchor into and infiltrate the host cell.
How do mutations empower my transmissibility and immune-evasion? Now, what I will describe to you will become very complicated, but I want to assure you that I am sharing with you the secret of what makes me, me. The answer is a set of over 13 mutations in my S-protein: T19R, (V70F*), T95I, G142D, E156-, F157-, R158G, (A222V*), (W258L*), (K417N*), L452R, T478K, D614G, P681R, D950N.
Of these, consider D614G, P681R, L452R, and T478K as the four horsemen of the apocalypse that make me uniquely destructive. The D614G mutation involves replacing the polar amino acid aspartic acid with a non-polar amino acid glycine. This alteration detaches the region involving S1/S2, making it more vulnerable to the action of proteases. Similarly, the P681R mutation changes the acidity of the furin cleavage
site. The L452R mutation replaces a neutral amino acid with a charged amino acid. Lastly, the T478K mutation replaces the non-charged amino acid with a charged amino acid. Together, these four mutations
strengthen the RBD-ACE-2 interaction, make the S1/S2 regions more prone to action by proteolytic enzymes, and reduce the access of pre-existing antibodies to key regions of the S-protein.
So, what does the future look like? Well, for me, the answer depends on you. First, the longer I persist in your communities, the longer I will keep acquiring new mutations in my S-protein. Have you heard of Delta plus? That is my next iteration that is gaining ground in the United Kingdom. Ergo, your first aim should be to contain and eliminate my circulation in your community.
How do you do that? The answer is simple- my reach depends on your behavior. I could disappear, assuming humans wear masks, maintain social distancing, and get vaccinated. On the other hand, if humans fail to regard these measures, I will thrive as an endemic nuisance in your communities.
In summary, you must realize that I am a virus- a microscopic entity that can neither think for itself nor spread by myself. If I am circulating and persisting in your community, it is because you allow me to. So, do the right thing- mask, socially distance, and vaccinate yourself.
Respectfully,
The Delta Variant
Legend:
Coronaviruses are characterized by the presence of spikes on their viral membrane. Each spike has two subunits- S1 and S2.
The S1 subunit binds with the receptors found on host cells and the S2 subunit is responsible for membrane fusion between viral envelope and the host cell. Within S1, the receptor binding domain (RBD) in involved
in binding to the host ACE- 2 receptor and is a target of neutralizing antibodies.
Fourth Quarter 2021 Detroit Medical News 9